Approximately 20 million units of blood components are transfused in the United States each year. Transfusion-associated acute lung injury (TRALI) is increasingly recognized as an important cause of transfusion-induced adverse events. The incidence and mechanisms of severe TRALI will be studied in Project 1. In addition to severe TRALI, recent studies suggest that mild to moderate lung injury (TRALI) is also caused by transfusions of blood products, especially in patients with underlying medical and surgical disorders. The lack of well-designed prospective studies has limited progress in evaluating mild to moderate TRALI. Therefore, the goals of this project are (1) to determine if TRALI exists as a spectrum of pulmonary dysfunction, rather than exclusively as a severe form of lung injury; (2) to determine the influence of elevated concentrations of cytokines and lyso-phosphatidyl choline in the plasma of stored red cells or platelets on pulmonary function; and (3) and to determine if an event prior to transfusion ("first event") is necessary before transfusion results in pulmonary dysfunction. These aims will be accomplished by prospective randomized clinical studies in humans with a wide range of risk for pulmonary dysfunction, using sensitive measures of lung injury including normal controls, patients undergoing major surgery, and critically ill patients who require mechanical ventilation. Data from these prospective, randomized studies will generate valuable new information regarding the scope and etiology of TRALI in humans, and will thereby provide important guidelines regarding preparation and administration of blood product transfusions hi several patient populations.